title: HIV-1 infection and alcohol abuse: neurocognitive impairment, mechanisms of neurodegeneration and therapeutic interventions.
abstract: Clinical studies indicate that alcohol dependence has an additive effect on cognitive deficits associated with HIV-1 infection. Findings in humans and animal models suggest that alcohol, similar to HIV-1, induces inflammatory processes in the brain leading to neurodegeneration. The causes of HIV-1-associated neurotoxicity are comparable to those mediating alcohol-induced neuronal injury. This review aims to present the mechanisms of the combined effects of HIV-1 and alcohol abuse in the brain and to discuss neuroprotective therapies. Oxidative stress, overproduction of pro-inflammatory factors, impairment of blood-brain barrier and glutamate associated neurotoxicity appear to play important roles in alcohol driven neurodegeneration. Diminution of neuroinflammation constitutes a logical approach for prevention of HIV-1 and alcohol mediated neurodegeneration. Agonists of cannabinoid receptor 2 (CB₂) possess potent anti-inflammatory and neuroprotective properties. We address multifaceted beneficial effects of CB₂ activation in the setting of HIV-1 brain infection and alcohol abuse.
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA. yuri.persidsky@tuhs.temple.edu
authors.forename: Yuri
authors.initials: Y
authors.lastname: Persidsky
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
authors.forename: Raghava
authors.initials: R
authors.lastname: Potula
authors.forename: Mary E
authors.initials: ME
authors.lastname: Abood
authors.forename: Ellen
authors.initials: E
authors.lastname: Unterwald
authors.forename: Ronald
authors.initials: R
authors.lastname: Tuma
mesh_terms: D000437:Alcoholism / Q000150:complications* / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003071:Cognition; D015658:HIV Infections / Q000150:complications* / Q000473:pathology; D006801:Humans; D009410:Nerve Degeneration / Q000150:complications* / Q000473:pathology